1. Field of the Invention
The present invention relates to a method and apparatus for the analysis of blood or other liquids by mass spectrometry to determine the partial pressures of gases and other volatile substances dissolved in the blood or other liquid, and more particularly, to a countercurrent membrane exchanger for equilibrating a carrier fluid with the sample of blood or other liquid, coupled to a tubular direct insertion membrane probe type of membrane inlet mass spectrometer.
2. Description of the Prior Art
Countercurrent exchange has been widely applied in the fields of heat transfer (for example countercurrent heat exchangers) and mass transfer (for example countercurrent dialysers). Prior applications have used countercurrent exchange to obtain maximal heat or mass transfer in the most efficient way possible, where the objective has been to achieve the smallest exchange area, smallest exchanger size, or minimal energy requirements to drive the liquid flow, for a given exchange rate. No prior use of countercurrent exchange, however, for the purpose of equilibrating a carrier stream gas partial pressure with a sample stream gas partial pressure, specifically to allow measurement of gas partial pressure in the sample with no dependence on gas solubility in the sample, is known to the inventors. The design of a countercurrent exchanger for this analytic purpose (measuring gas partial pressures in liquid samples) is quite different from the design of countercurrent exchangers for maximal transfer rates. More specifically, the inventors are not aware of any prior use of a membrane countercurrent exchanger for the purpose of measuring the partial pressures of gases and other volatile substances in blood, or other fluids, with no dependence on the solubility of the gas or volatile substance in the blood or other fluid.
In the current invention, the partial pressures of gases and volatile substances in the carrier fluid (which has exited the countercurrent membrane exchanger) are measured by use of a tubular direct insertion membrane probe (t-DIMP) as an inlet to a mass spectrometer. Considerable work has been done by others in the area of t-DIMP. For example, Kotiaho et al. describe in an article entitled “Membrane Introduction Mass Spectrometry,” Anal. Chem., Vol 63, No. 18, pp. 875A–883A (Sep. 15, 1991) the application of t-DIMP in volatile organic chemical (VOC) analysis and fermentation monitoring. However, no reference can be found relating to the use of Teflon™ sleeves specifically to reduce noise, to the use of radiation shields to allow lower carrier flow rates, and to the heating of the section between the ion source and the vacuum pumps specifically to improve linearity.
Measurement of gas partial pressures in liquid samples has applications in fermentation monitoring, VOC analysis, and in the multiple inert gas elimination technique (MIGET). In the MIGET, gas partial pressures in blood samples are used to define the distribution of ventilation/perfusion ratios in the lung, allowing precise definition of the mechanisms of impaired pulmonary gas exchange. The closest technology similar to the current invention known to the inventors is an attempt to perform rapid MIGET by mass spectrometry (MIGET-MS) by Mastenbrook, Massaro, and Dempsey in the late 1970's and early 1980's. Mastenbrook et. al. published a description of membrane inlet mass spectrometry (MIMS) probes for use in MIGET in blood samples in an article entitled “Ventilation-Perfusion Ratio Distributions By Mass Spectrometry With Membrane Catheters,” J. Appl. Physiol., Vol. 53, pp. 770–778 (1982). The membranes they used, commercially available at the time, sampled enough gas from the blood phase to introduce what is known as stirring artifact, referring to the difference in signal between a gas phase and a liquid phase owing to the diffusional resistance in unstirred liquid layers. They suggested calibrating to account for stirring artifact, but because stirring artifact is a function of the gas solubility in blood, this would require a separate calibration for each individual subject. In other words, their design did not overcome the need to equilibrate at least one blood sample per subject with a gas phase to determine solubility, which is the main source of error and analysis time in the traditional MIGET by gas chromatography (MIGET-GC). In addition, they did not specify the time response of their system, but because of the strong adsorption of acetone and diethyl ether to room temperature stainless steel, it is believed that the response speed for these gases would likely be very slow. No further development of this technology has been found by the present inventors.
It is desired to develop a technique for measuring gas partial pressures in liquids, such as blood, which is independent of the solubility of the gas in the sample and thus much more accurate than existing gas partial pressure measurement techniques. The present invention has been designed to meet this need in the art.